Corneal ulceration with subsequent inflammation and scarring is a major cause of blindness in the world. Corneal ulceration occurs in the rare human autosomal recessive metabolic disease, tyrosinemia II. Increased plasma tyrosine levels are related to hepatic tyrosine aminotransferase deficiency. Using a rat model, early corneal epithelial cells contained birefringent needle-shaped crystals (presumably tyrosine) and increased lysosomal enzymes. Later neutrophils infiltrated the lesions. While it is hypothesized that intracellular tyrosine crystals initiate the inflammatory cascade, the molecular mechanism(s) of the localized corneal inflammatory response is unknown. The animal model will be rats fed a low-protein diet + 5 percent tyrosine. The applicant proposes first to determine if the crystalline deposits are indeed tyrosine. Using x-ray powder diffraction crystallography, the microcrystalline structure of these corneal deposits will be defined. Next, the applicant will determine if the crystals induce a chemotactic factor. Media of short-term enucleated eye cultures from both groups will be tested for chemotactic activity, using the Boyden chamber and rat peritoneal neutrophils. To test phlogistic potential, those culture media containing chemotactic activity will be tested for their ability to release lysosomal enzymes and superoxide anion from rat peritoneal neutrophils. Improved knowledge of the pathogenesis of tyrosine crystal-host interaction should permit development of methods to modulate corneal inflammation and thus prevent further corneal destruction and subsequent blindness. Such knowledge will also shed light on other crystal-associated diseases.